Work

Polyethylene terephthalate microplastics impair erectile function through macrophage mediated cGAS-STING ferroptosis

Year: 2026

Type: article

Abstract: Microplastic pollution is a global concern, yet its impact on male reproductive health remains unclear. We assessed chronic polyethylene terephthalate (PET) microplastic exposure using human corpus cavernosum (CC) tissues, a rat model, and cell assays. MPs were quantified in CC from 10 patients; those with erectile dysfunction (ED) showed a higher MP burden, with PET predominant. In rats, chronic PET-MP exposure dose-dependently impaired erectile function, increased fibrosis, and reduced smooth muscle. Mechanistically, PET-MPs localized to macrophage mitochondria, causing depolarization and ROS generation, mtDNA leakage, cGAS-STING activation, and macrophage ferroptosis. This ferroptotic signaling amplified inflammation, promoted M1 polarization, and triggered endothelial-to-mesenchymal transition, leading to vascular dysfunction and ED. Depleting macrophages or inhibiting cGAS-STING or ferroptosis reduced inflammation and partially rescued erectile responses. Together, these data identify a cGAS-STING-ferroptosis axis linking environmental MP exposure to ED and suggest upstream innate-immune and ferroptosis pathways as therapeutic targets.

Source: iScience

DOI: 10.1016/j.isci.2026.115044